Healthy
Conditions
Keywords
Non-small cell lung cancer (NSCLC), P-glycoprotein, Tepotinib, Dabigatran Etexilate
Brief summary
This study investigated the effect of Tepotinib on the pharmacokinetics (PK) of the p-glycoprotein (P-gp) probe substrate Dabigatran etexilate.
Interventions
DRUGDabigatran Etexilate
Participants received single oral dose of Dabigatran etexilate on Day 1 of Treatment period 1 and co-administration of Dabigatran with Tepotinib on Day 8 of Treatment period 2.
DRUGTepotinib
Participants received single oral dose of Tepotinib for 8 days in Treatment period 2.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NA
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 44 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy participants of non-child bearing potential * Body weight between 50 to 100 kilogram (kg) * Body mass index (BMI) between 18.5 and 29.9 kilogram per meter square (kg/m\^2) * A male participant must agree to use and to have his female partner of childbearing potential to use highly effective method of contraception * Participant must have given written informed consent before any study-related activities * All values for hematology, coagulation, and biochemistry tests of blood and urinalysis are within the normal range. Minor (solitary) non-clinically relevant deviation(s) are allowed as judged by the Investigator * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Participation in a clinical study within 60 days prior to first drug administration * Whole blood donation or loss of \> 450 milliliter (mL) within 60 days prior to first drug administration * Any surgical or medical condition, or any other significant disease that could interfere with the study objectives, conduct, or evaluation * Supine systolic blood pressure (SBP) greater than (\>) 140 millimeter of mercury (mmHg) or less than (\<) 90 mmHg, diastolic blood pressure (DBP) \> 90 or \< 50 mmHg, and pulse rate \> 90 or \<50 beats per minute (bpm) at Screening and at admission on Day-1. * 12-Lead electrocardiograms (ECG) showing a corrected QT interval per Fridericia's formula (QTcF) \> 450 milliseconds (ms), PR \> 215 ms, or QRS \> 120 ms (at Screening) * Creatinine clearance estimated glomerular filtration rate (eGFR) \< 90 milliliter per minute (mL/min) (at Screening) * Participants with gall bladder removal or other relevant surgery of gastrointestinal tract * History of any malignancy * History of epilepsy * Ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or excipients * Participants who in the Investigator's judgment were perceived as having an increased risk of bleeding * Positive screen for alcohol or drugs of abuse (at Screening and Day -1) * Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV), and human immunodeficiency virus 1 and 2 antibodies (HIV1/HIV2 antibodies) (at Screening) * Excessive consumption of xanthine-containing food or beverages before study drug administration until collection of last pharmacokinetic (PK) sample in each period (at Screening and Day -1) * Receipt of any prescription or nonprescription medication within 14 days or 5 half-lives, before study drug administration * Smoker or former smoker who stopped smoking less than 6 months before the time of the Screening Visit * Intake of grapefruit, Seville orange, cranberry or juices of these 3 fruits, or St. John's Wort, from 14 days prior to Day -1 * Inability to communicate or cooperate with the Investigator * Other factors, which in the opinion of the Investigator may interfere with study conduct (at Screening and Day -1 of first Period only) * Legal incapacity or limited legal capacity * Participants kept in detention * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Total Dabigatran | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8 | AUC0-t was calculated according to the mixed log linear trapezoidal rule. |
| Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Total Dabigatran | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8 | AUC0-inf was calculated as AUC0-t plus (+) AUCextra. AUCextra represents the extrapolated part of AUC0-inf calculated by Clastpred/Lambda z, where Clastpred is the predicted plasma concentration at the last sampling time point, calculated from the log-linear regression line for Lambda z determination at which the measured plasma concentration is at or above Lower limit of quantification (LLOQ). |
| Maximum Observed Plasma Concentration (Cmax) of Total Dabigatran | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8 | Cmax was obtained directly from the concentration versus time curve. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Plasma Concentration (Tmax) of Total Dabigatran | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8 | Tmax is time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve. |
| Elimination Half Life (t1/2) of Total Dabigatran | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8 | Elimination Half Life (t1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. |
| Apparent Clearance (CL/f) of Total Dabigatran | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. |
| Apparent Volume of Distribution During Terminal Phase (Vz/f) of Total Dabigatran | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8 | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/f after oral dose was influenced by the fraction absorbed. |
| Percentage of Area Under the Plasma Concentration-Time Curve From Time Tlast Extrapolated to Infinity (AUC0-inf) Obtained by Extrapolation (AUCextra%) of Total Dabigatran | Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8 | The AUC from time tlast extrapolated to infinity given as percentage of AUC0-inf. AUCextra% = (AUCextra /AUC0-inf)\*100. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Screening up to Day 4 in Period 1; Day 1 up to Day 15 in Period 2 | Adverse event (AE) was defined as any untoward medical occurrence in participants which does not necessarily have causal relationship with treatment. AE was any unfavorable and unintended sign (including abnormal laboratory finding), symptom/disease temporally associated with use of medicinal product, whether/not considered related to medicinal product. A serious adverse event (SAE) was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE is defined as AEs starting/worsening after first intake of the study drug. TEAEs included both serious TEAEs and non-serious TEAEs. |
| Number of Participants With Clinically Significant Changes in Laboratory Values | Screening up to Day 4 in Period 1; Day 1 up to Day 15 in Period 2 | Number of participants with clinically significant change in laboratory values were reported. Clinical significance was decided by the investigator. Laboratory investigation included hematology, biochemistry, virology, drugs of abuse, hormones, urinalysis, and coagulation. |
| Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Findings | Screening up to Day 4 in Period 1; Day 1 up to Day 15 in Period 2 | Number of participants with clinically significant change in 12-lead ECG were reported. Clinical significance was decided by the investigator. The 12-lead ECGs were recorded after the participant have rested for at least 5 minutes in supine position. |
| Number of Participants With Clinically Significant Changes in Vital Signs | Screening up to Day 4 in Period 1; Day 1 up to Day 15 in Period 2 | Number of participants with clinically significant change in vital signs were reported. Clinical significance was decided by the investigator. Vital signs included body temperature, blood pressure, and pulse rate. |
Countries
Germany
Participant flow
Pre-assignment details
Overall, 39 participants were screened in this study. Out of which, 20 participants received Dabigatran and Tepotinib + Dabigatran treatment.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants who received a single oral dose of 75 mg dabigatran etexilate capsule in treatment period 1 and 500 mg tepotinib (500 mg) film coated tablet from Day 1 to 8 along with 75 mg dabigatran etexilate Capsule in treatment period 2 under fed state. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 2 | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 33 Years STANDARD_DEVIATION 8.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 4 / 20 | 15 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Area Under Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Total Dabigatran
AUC0-t was calculated according to the mixed log linear trapezoidal rule.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8
Population: Pharmacokinetic (PK) analysis set: all participants who completed at least 1 period without any relevant protocol violations with respect to factors affecting comparability of PK results with adequate study drug compliance and evaluable dabigatran PK data. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate | Area Under Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Total Dabigatran | 461 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 74.9 |
| Tepotinib + Dabigatran | Area Under Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Total Dabigatran | 709 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 64.6 |
90% CI: [127.35, 179.93]
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Total Dabigatran
AUC0-inf was calculated as AUC0-t plus (+) AUCextra. AUCextra represents the extrapolated part of AUC0-inf calculated by Clastpred/Lambda z, where Clastpred is the predicted plasma concentration at the last sampling time point, calculated from the log-linear regression line for Lambda z determination at which the measured plasma concentration is at or above Lower limit of quantification (LLOQ).
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8
Population: PK analysis set: all participants who completed at least 1 period without any relevant protocol violations with respect to factors affecting comparability of PK results with adequate study drug compliance and evaluable dabigatran PK data. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Total Dabigatran | 544 ng*hr/mL | Geometric Coefficient of Variation 32.8 |
| Tepotinib + Dabigatran | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Total Dabigatran | 730 ng*hr/mL | Geometric Coefficient of Variation 61.8 |
90% CI: [122.89, 170.39]
Primary
Maximum Observed Plasma Concentration (Cmax) of Total Dabigatran
Cmax was obtained directly from the concentration versus time curve.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8
Population: PK analysis set: all participants who completed at least 1 period without any relevant protocol violations with respect to factors affecting comparability of PK results with adequate study drug compliance and evaluable dabigatran PK data. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate | Maximum Observed Plasma Concentration (Cmax) of Total Dabigatran | 54.5 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 72.8 |
| Tepotinib + Dabigatran | Maximum Observed Plasma Concentration (Cmax) of Total Dabigatran | 76.9 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 61.8 |
90% CI: [121.59, 157.65]
Secondary
Apparent Clearance (CL/f) of Total Dabigatran
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8
Population: PK analysis set: all participants who completed at least 1 period without any relevant protocol violations with respect to factors affecting comparability of PK results with adequate study drug compliance and evaluable dabigatran PK data. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate | Apparent Clearance (CL/f) of Total Dabigatran | 138 Liter per hour (L/h) | Geometric Coefficient of Variation 32.8 |
| Tepotinib + Dabigatran | Apparent Clearance (CL/f) of Total Dabigatran | 103 Liter per hour (L/h) | Geometric Coefficient of Variation 61.8 |
Secondary
Apparent Volume of Distribution During Terminal Phase (Vz/f) of Total Dabigatran
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/f after oral dose was influenced by the fraction absorbed.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8
Population: PK analysis set: all participants who completed at least 1 period without any relevant protocol violations with respect to factors affecting comparability of PK results with adequate study drug compliance and evaluable dabigatran PK data. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate | Apparent Volume of Distribution During Terminal Phase (Vz/f) of Total Dabigatran | 1627 Liter | Geometric Coefficient of Variation 34.7 |
| Tepotinib + Dabigatran | Apparent Volume of Distribution During Terminal Phase (Vz/f) of Total Dabigatran | 1157 Liter | Geometric Coefficient of Variation 58.4 |
Secondary
Elimination Half Life (t1/2) of Total Dabigatran
Elimination Half Life (t1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8
Population: PK analysis set: all participants who completed at least 1 period without any relevant protocol violations with respect to factors affecting comparability of PK results with adequate study drug compliance and evaluable dabigatran PK data. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate | Elimination Half Life (t1/2) of Total Dabigatran | 8.18 Hour | Geometric Coefficient of Variation 12.9 |
| Tepotinib + Dabigatran | Elimination Half Life (t1/2) of Total Dabigatran | 7.81 Hour | Geometric Coefficient of Variation 13.5 |
Secondary
Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Findings
Number of participants with clinically significant change in 12-lead ECG were reported. Clinical significance was decided by the investigator. The 12-lead ECGs were recorded after the participant have rested for at least 5 minutes in supine position.
Time frame: Screening up to Day 4 in Period 1; Day 1 up to Day 15 in Period 2
Population: The safety analysis set included all participants who received at least 1 dose of the planned IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dabigatran Etexilate | Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
| Tepotinib + Dabigatran | Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Laboratory Values
Number of participants with clinically significant change in laboratory values were reported. Clinical significance was decided by the investigator. Laboratory investigation included hematology, biochemistry, virology, drugs of abuse, hormones, urinalysis, and coagulation.
Time frame: Screening up to Day 4 in Period 1; Day 1 up to Day 15 in Period 2
Population: The safety analysis set included all participants who received at least 1 dose of the planned IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dabigatran Etexilate | Number of Participants With Clinically Significant Changes in Laboratory Values | 0 Participants |
| Tepotinib + Dabigatran | Number of Participants With Clinically Significant Changes in Laboratory Values | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Vital Signs
Number of participants with clinically significant change in vital signs were reported. Clinical significance was decided by the investigator. Vital signs included body temperature, blood pressure, and pulse rate.
Time frame: Screening up to Day 4 in Period 1; Day 1 up to Day 15 in Period 2
Population: The safety analysis set included all participants who received at least 1 dose of the planned IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dabigatran Etexilate | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Tepotinib + Dabigatran | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Adverse event (AE) was defined as any untoward medical occurrence in participants which does not necessarily have causal relationship with treatment. AE was any unfavorable and unintended sign (including abnormal laboratory finding), symptom/disease temporally associated with use of medicinal product, whether/not considered related to medicinal product. A serious adverse event (SAE) was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE is defined as AEs starting/worsening after first intake of the study drug. TEAEs included both serious TEAEs and non-serious TEAEs.
Time frame: Screening up to Day 4 in Period 1; Day 1 up to Day 15 in Period 2
Population: The safety analysis set included all participants who received at least 1 dose of the planned investigational medicinal product (IMP).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dabigatran Etexilate | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 0 Participants |
| Dabigatran Etexilate | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Tepotinib + Dabigatran | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Treatment-emergent Adverse Events (TEAEs) | 15 Participants |
| Tepotinib + Dabigatran | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 0 Participants |
Secondary
Percentage of Area Under the Plasma Concentration-Time Curve From Time Tlast Extrapolated to Infinity (AUC0-inf) Obtained by Extrapolation (AUCextra%) of Total Dabigatran
The AUC from time tlast extrapolated to infinity given as percentage of AUC0-inf. AUCextra% = (AUCextra /AUC0-inf)\*100.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8
Population: PK analysis set: all participants who completed at least 1 period without any relevant protocol violations with respect to factors affecting comparability of PK results with adequate study drug compliance and evaluable dabigatran PK data. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate | Percentage of Area Under the Plasma Concentration-Time Curve From Time Tlast Extrapolated to Infinity (AUC0-inf) Obtained by Extrapolation (AUCextra%) of Total Dabigatran | 3.03216 percentage of AUC0-inf | Geometric Coefficient of Variation 55.1249 |
| Tepotinib + Dabigatran | Percentage of Area Under the Plasma Concentration-Time Curve From Time Tlast Extrapolated to Infinity (AUC0-inf) Obtained by Extrapolation (AUCextra%) of Total Dabigatran | 2.3654 percentage of AUC0-inf | Geometric Coefficient of Variation 63.8621 |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of Total Dabigatran
Tmax is time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours Post-dose on Day 1 and Day 8
Population: PK analysis set: all participants who completed at least 1 period without any relevant protocol violations with respect to factors affecting comparability of PK results with adequate study drug compliance and evaluable dabigatran PK data. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dabigatran Etexilate | Time to Reach Maximum Plasma Concentration (Tmax) of Total Dabigatran | 3.00 Hour |
| Tepotinib + Dabigatran | Time to Reach Maximum Plasma Concentration (Tmax) of Total Dabigatran | 4.00 Hour |
90% CI: [-0.3, 1]